Head and neck cancer, particularly squamous cell carcinoma (SCC) of the upper aerodigestive tract, poses difficult diagnostic and therapeutic challenges to the clinician. A methodical approach, including complete visualization of mucosal surfaces, appropriate imaging, and tissue diagnosis whenever possible, gives patients the best opportunity for early intervention. A treatment program of surgery, radiation, or chemotherapy is best developed by a devoted head and neck oncologic team, involving surgeons, radiation and medical oncologists, and rehabilitative specialists with significant experience in the care of head and neck oncologic patients. Despite new advancements in the treatment of patients with advanced stage SCC of the head and neck, little progress has been made in overall survival. Several new avenues of investigation are currently being explored, one of which may ultimately provide the answer for this devastating disease.